Coagulometer

ABSTRACT

AN APPARATUS FOR DETERMINING THE COAGULATION TIME OF BLOOD AND OTHER LIQUIDS WHICH HAS A MOTOR DRIVEN ROTATING STIRRER THAT IS MOUNTED FOR VERTICAL MOVEMENT ON A BASE BELOW WHICH IS MOUNTED A ROTATABLE INDEXING SUPPORT MEMBER BEARING LIQUID SAMPLES. A MANUALLY OPERABLE RACK IS USED TO INSERT THE STIRRER IN T HE C ONTAINERS AND TO START THE MOTOR TO ROTATE THE STIRRER. A SLIP SWITCH IS USED TO BREAK THE CIRCUIT WHEN THE STIRRER ENCOUNTERS RESISTANCE CAUSED BY THE COAGULATION. THE TIME FOR COAGULATION IS READ DIRECTLY OFF A COUNTER ATTACHED TO THE MOTOR.

NOV. 28 c SANZ I COAGULOMETER Filed March 17-. 1970 v 4 Sheets-Sheet 1FIG. I

4 Sheets-Shed 2 M. C. SANZ COAGULOMETER Nov. 28, 1972 Filed March 17,1970 M. c. SANZ COAGULOMETER Nov. 28, 1972 4 Sheets-Sheet Filed March17, 1970 M. C. SANZ COAGULOMETER Nov. 28, 1972 4 Sheets-Sheet 4 FiledMarch 17, 1970 will? United States Patent 3,704,099 COAGULOMETER ManuelClaude Sanz, Geneva, Switzerland, assignor to Micromedic Systems, Inc.,Philadelphia, Pa. Filed Mar. 17, 1970, Ser. No. 20,341 Claims priority,application Switzerland, Mar. 19, 1969, 4,124/ 69 Int. Cl. G01n 11/14,33/16, 33/26 U.S. Cl. 23253 R 11 Claims ABSTRACT OF THE DISCLOSURE Thisinvention provides apparatus for measuring the coagulation time of ablood sample.

The coagulation of human blood is the result of a particularly complexprocess of a biochemical nature which calls into play a dozen componentscalled factors, conventionally denoted by means of Roman numerals I, II,III, etc.

The absence or deficiency of one or more of these factors causes, in thehuman body, the coagulation of the blood to deteriorate or even tobecome impossible in certain cases and almost always causes more or lessacute ailments in certain parts of the body, in particular the liver, aswell as certain defects in the metabolism.

The detection of the factors which may be deficient or absent in bloodis clearly very important, whether it be for the purpose of deciding themost appropriate treatment for eliminating or circumscribing certainailments that may have been observed in a subject, or, as aprecautionary measure, before any surgical operation, for avoiding, forexample, haemorrhages.

This detection is also of particular importance in respect of thetreatment to be given to patients suifering from a thrombosis and towhom it is necessary to administer anticoagulants in a quantity whichmust clearly be determined after taking into account the abnormalfactors which were the cause of the thrombosis.

Among the numerous tests which are performed to carry out thisdetection, that proposed by A. Quick is one of the simplest and swiftestto make. This test which is essentially intended to show up anyconcentration deficiency of the factors I, II, V, VII and X of theblood, is broadly speaking carried out in the following manner: afteradding a solution of anticoagulant (solution of trisodium citrate orsodium oxalate) to freshly drawn blood, thereby removing from the bloodthe Ca++ ions (factor IV) and preventing coagulation thereof, themixture is subjected to a centrifugal operation and the plasma whichcomes to float is drawn off. To this floating plasma is then added anequal quantity of a suspension of thromboplastine (a tissue extract of akind corresponding to that of factor III of the blood) and the mixtureis brought 3,704,099 Patented Nov. 28, 1972 to a temperature of 37 C.Into this mixture is then introduced a solution of calcium chloride (toadd Ca++ ions), also brought to 37 C., and the coagulation time of theresulting composite liquid is measured.

According to one variant of this test, proposed by Soulier, it ispossible to replace the floating plasma by natural freshly drawn blood.

If the concentration of the factors I, II, V, VII and X of the testedblood is normal, the coagulation time is of the order of 10 to 15seconds, according to the activity of the thromboplastine used. On theother hand, a coagulation time greater than the 'value obtained withnormal blood indicates a deficiency of one or more factors without,however, indicating which one; other kinds of tests enable these factorsto be identified.

The measurement of this coagulation time, originally eifected by meansof a simple chronometer which an operator stopped in an empiric manner,on the basis of a visual estimation of the state of coagulation reachedby the composite liquid under examination, has for sometime been carriedout automatically by means of various forms of apparatus.

In U.S. patent specification No. $053,078 there is disclosed anapparatus consisting of a viscometer which comprises a rotating feelerthat dips into the composite liquid to be tested, this liquid beingcontained in a device that is rotated at constant speed. With thisfeeler is associated an electric switch for controlling the electricsupply of the motor that drives the container and of a time counter.This switch is adapted to open under the action of the feeler when theviscosity of the liquid being tested reaches a predetermined value,corresponding to a particular state of coagulation of the blood or ofthe plasma, depending on the nature of the composite liquid beingtested, the feeler being then moved angularly forward by the thickeningliquid to an extent sufficient to actuate the switch. The reading whichis then given by the time counter corresponds to the coagulation time ofthe blood or of the plasma being tested.

In the published specification of Dutch patent application No. 68/14,790 there is disclosed another form of apparatus for measuring bloodcoagulation time. This form of apparatus involves the use of a containerdevice having three compartments of which the first contains a calciumsalt and the second contains thromboplastine, these two compartmentsbeing subsequently made to communicate with the third compartment, thislatter compartment being intended to receive the blood to be tested andcontaining a stirrer consisting of a magnetisable rod. This particularapparatus is also a viscometer and comprises a support for the containerdevice, a rotary magnet, a magnetisable armature extending from themagnet to near the third compartment of the container device mounted onthe support for driving the magnetisable stirring rod inside thiscompartment, a pick-off coil surrounding the armature and connected tothe terminals of an electronic device for detecting flux variations inthe coil, these variations being caused, during operation, by changes inthe position of the stirring rod in relation to the armature under theaction of the increasing viscosity of the liquid in which the stirringrod is required to move, this increasing viscosity being due to thecoagulating blood.

In the specification of our co-pending patent application No. 20,340filed Mar. 17, 1970, we have described a container device for carryingout a blood coagulation test which includes two superposed enclosuresthat are separated from one another by a removable partition, the firstenclosure being intended to receive a blood sample and containing asuspension of at least one of the blood coagulation factors in asolution of anticoagulant whereas the other enclosure contains a calciumsalt solution, and which further includes a stirrer defining a wallportion which lies opposite the partition and which forms part of theupper enclosure, said wall portion being de tachable from the remainderof the upper enclosure and the stirrer having a substantially upstandingactuating rod projecting above the upper enclosure.

As described in the specification of this co-pending patent application,the device, to become operative, involves introducing a metered quantityof blood into the first enclosure, heating the contents of bothenclosures to 37 C., exerting on the stirrer rod sufficient pressure tointroduce the stirrer first into the first enclosure and then into thesecond upon removal of the partition, rotating the stirrer thereby inparticular homogeneously to mix the liquid contents of the twoenclosures, and determining the amount of time that elapses between themoment when the two enclosures are made to communicats with one anotherand the moment when the resistive torque acting on the stirrer, due tothe viscosity of the composite liquid in the device, reaches apredetermined value that corresponds to a particular state ofcoagulation of the blood contained in this liquid.

An object of the invention is to provide an apparatus for automaticallymeasuring the coagulation time of a blood sample in a container deviceof the kind set forth, with reference to our co-pending patentapplication.

The apparatus proyided by the present invention comprises a rotaryassembly mounted for rotation about a vertical axis, an electric motorfor rotatably driving said assembly, means for measuring the duration ofthe rotary driving action of the motor, a switch associated androtatable with said rotary assembly for controlling the supply ofelectric current to the measuring means and to the motor, a support fora sample-containing device located beneath the rotary assembly in aposition such that the longitudinal axis of the stirrer rod of saidsamplecontaining device when placed on the support may lie in axialalignment with the rotational axis of said rotary assembly, a pinassociated with said rotary assembly coaxially with the rotational axisthereof, said pin being mounted for pivotal movement about said axis,means for releasably coupling the lower end of the pin to said stirrerrod, a pin-positioning finger rigid with said pin, first and secondabutments arranged to cooperate with said finger to define a firstextreme angular position for the pin in relation to the rotary assemblyand a second extreme angular position for the pin situated past thefirst position in relation to the direction in which the drive motorrotates said assembly, a member for actuating said switch which iskinematically rigid with said pin and which is adapted to close saidswitch when the pin is in its firstextreme angular position, and amember for holding the pin in said first extreme angular position for aslong as any resistive torque on the pin opposing rotation of saidassembly remains below a certain value; wherein said pin is axiallyslidable in relation to the rotary assembly; wherein said assemblyincludes a tubular member of insulating material coaxial with therotational axis of the assembly and surrounding said pin over part ofits length, said tubular member having a longitudinal slot formed in thewall thereof into which extends said pinpositioning finger and of whichthe edges that define the upper and lower ends thereof respectivelyprovide third and fourth abutments arranged to cooperate with saidfinger to define a first extreme axial position for the pin in whichsaid pin lies remote from any sample-containing device on said supportand a second extreme axial position for the pin in which said pin, aftercoming into engagement with the stirred rod of a sample-containingdevice on said support through said coupling means and after removal ofsaid partition and of said wall portion, holds said stirrer depressed inthe enclosures of said de vice; wherein one longitudinal edge of saidslot extends vertically over its entire length and forms, along thelower portion thereof, said first abutment, and the other longitudinaledge of the slot includes a first portion extending vertically from thetop edge of the slot to provide the pin-positioning finger incooperation with the corresponding portion of said one longitudinal edgewith a rectilinear path of travel over the major part of itsdisplacement between said third and fourth abutments thereby to holdsaid pin in its first extreme angular position over a correspondinglength of its axial displacement between said extreme axial positions,and a second portion which is offset in relation to the first towardsthe bottom edge of the slot and which forms therealong said secondabutment; wherein said switch-actuating member is formed by saidpin-positioning finger; wherein said switch includes a resilient contactblade which normally occupies an inoperative, rest, positioncorresponding to the open position of the switch and which is adapted tobe flexed into an operative position corresponding to the closedposition of the switch, said blade having an engageable part whichprojects inwardly into said slot, when said blade is in its inoperativeposition, in a portion of the slot corresponding to the locationoccupied by said pin-positioning finger when the latter bears bothagainst said one longitudinal edge and said bottom edge of the slot, andto a depth sufiicient to enable said resilient blade to be flexed bysaid finger into said operative position upon said finger being moved tosaid location; and wherein it further comprises a push-member,kinematical- 1y rigid with said pin, for slidably moving said pinbetween said first and second extreme axial position.

In the accompanying diagrammatic drawings:

FIG. 1 is a side elevation of one form of embodiment of the apparatusprovided by the invention;

FIG. 2 is a plan view of the apparatus shown in FIG. 1 without itscover;

FIG. 3 is a section through the apparatus shown in FIGS. 1 and 2, alongline III-III of FIG. 2;

FIG. 4 is'a section through a detail of the apparatus shown in FIGS. 1to 3, on a larger scale, along the line IVIV of FIG. 2;

FIG. 5 is a view similar to that of FIG. 4 but showing certaincomponents in different relative positions;

FIG. 6 is a cross-section along line VI-VI of FIG. 4;

FIG. 7 represents the detail of FIG. 4 viewed in the direction of arrowA, some of the components being shown in elevation and others beingshown in section;

FIG. 8 is a diagram of the electrical circuitry in the apparatus shownin FIGS. 1 to 2; and

FIGS. 9, l0 and 11 illustrate three stages in the operation of theapparatus shown in FIGS. 1 to 3 in conjunction with a sample-containingdevice.

' The illustrated apparatus is more particularly intended to carry outthe last two stages of a coagulometric test on a blood sample, thesestages being (a) the mixing of the blood with coagulation reactants and(b) the detection of a particular state of coagulation of the blood andthemeasurernent of the time taken by the blood being tested to reachthis state from the moment stage (a) has been carried out.

For this, the blood and the reactants that are required for itscoagulation are placed in container devices of the kind described in thespecification of our above identified co-pending patent application andof which one can be seen in axial section in FIGS. 9, 10 and 11.

As can in particular be seen from FIG. 9 and as described in detail inthe specification of our above mentioned application, these devicescomprise each two tubular elements 1 and 2, made for instance ofpolyethylene 0r polypropylene, that are interengageably assembledtogether and within which are provided three transverse partitions. Thefirst of these partitions is formed by the lower end of a rod 3,coaxially arranged inside element 1, and by a tearable annular membranewhich connects the edge of the lower end of rod 3 to the inner surfaceof element 1; the second partition is formed by a circular disc of whichthe edge is connected to the inner surface of element 2 by a tearableannular membrane also; and the third partition is formed by a disc 5which is forcefitted into the opening of element 2 some distance up thelatter.

These three partitions define within the assembled elements 1 and 2 afirst enclosure E that extends into both elements, and a secondenclosure E in element 2 only.

Enclosure E which is meant to receive the blood sample to be tested,contains a suspension of a blood coagulation factor in a solution of ablood anticoagulant. This may consist of a suspension of thromboplastinein a solution of trisodium citrate or of sodium oxalate.

Enclosure E contains a solution of a calcium salt, e.g. calciumchloride, which is chemically equivalent to the anticoagulant solutioncontained in enclosure E Also, the amount of solution in enclosure E isthe same as the amount of liquid in enclosure E It should be noted thatthe space occupied by the liquid in enclosure E is equal to at most halfthe total space in enclosure E, as the latter is also intended toreceive a quantity of blood to be tested equal to that of the aboveliquid.

As indicated in the specification of our aforementioned application, theabove container device is supplied ready for use, i.e. with enclosure Eand E already each containing their appropriate liquids.

Once the blood sample to be tested has been collected, the containerdevice is rapidly moved in an axial direction and abruptly stopped so asto bring all of the liquid contained in enclosure E into the portionthereof in element 1; the tubular elements 1 and 2 are then taken apartand a metered quantity of the blood to be tested is introduced into theother portion of enclosure E i.e. that in element 2, and the twoelements are then reassembled again. Since the Ca++ ions are fixed bythe trisodium citrate or the sodium oxalate, depending on theanticoagulant that is used for the suspension of coagulation factor inenclosure E the blood will not coagulate. Once this operation has beencompleted, use is made of the apparatus illustrated in FIGS. 1 to 3.

This apparatus comprises a casing formed by a rectangular base ofplastic material which rests on a support, not shown, by means ofpillars 11 and along the right hand edge of which is secured a verticalwall 12, also rectangular and of plastic material, carrying a switch 13to control the supply of electricity to the apparatus; the casingfurther comprises a cover 14 secured along the three free edges of thebase 10 and of the wall 12 by means of screws not shown.

On the base 10 is mounted a synchronous motor M with which is associatedreduction gearing D having an output shaft d connected to a horizontalshaft 15 by a resilient sleeve 16. This shaft 15 is rotatably mounted intwo flanges 17a and 17b of a frame 17 for a counter 18 secured to thebase 10 and having a set of numberbearing drums 19 which are driven offa toothed wheel 20, rigid with the shaft 15, and through theintermediary of a pinion 21 which controls the rotation of the firstdrum 19, the following drums of the set being each driven by thepreceding drum, in the usual manner.

As the counter 18 is directly coupled to the shaft 15 and therefore tothe motor M through the reduction gearing D, and as this motor is asynchronous motor rotating at practically constant speed, it is possibleto determine the length of time the motor M has rotated by reading thenumber indicated by the counter 18 at the end of such rotation, providedof course that the counter 18 has been set to zero before the motor Mbegins to rotate. If the first drum 19, starting from the left hand side(FIGS.

1 and 2) is numbered from 0 to 9, the second drum is numbered 0 to 5,the third 0 to 9 and the fourth 0 to 9 also, the meter 18 can give anindication corresponding to at most 9 minutes, 59 seconds and 9 tenthsof a second. The counter 18 can therefore be used to indicatecoagulation time in the case of the Quick test, since this time isnormally of the order of 10 to 15 seconds.

In order to set the counter 18 to zero, the pinion 21 must be rotated ina direction opposite to the normal direction of rotation under theaction of the toothed wheel 20. For this purpose, the shaft carrying thepinion 21 passes through the flange 17b of frame 17 and carries at itsfree end a pinion 22 which engages firstly, with a rack 23a rigid with avertical rod 23 and secondly, with a wheel 24. This wheel is rotatablymounted on an upstanding lug 24a rigid with the base 10 and meshes withan endless screw 25 carried by one end of a shaft 26 (FIG. 3).

The rod 23 has a length greater than the height of the casing of theapparatus and is mounted for vertical sliding movement in two apertures,one being provided in the base 10 and the other being provided in thetop of the cover 14 directly above the aperture in the base 10.

Above the rack 23a the rod 23 carries a horizontal arm 27 and, at itsupper end, a knob 28 by means of which the rod can be held and actuatedaxially between a first, lower, position as shown in FIG. 5 and asecond, upper, position in which the arm 27 comes close to the cover 14.The amplitude of this displacement is sufficient to set the counter 18to zero, this setting to zero operation being effected when the rod 23is moved from its upper position to its lower position.

At its free end opposite the coupling sleeve 16, the shaft 15 carries abevel gear 29 meshing with another bevel gear 30. Bevel gear 30 ismounted on a cylindrical root 31a of a tubular member 31 (FIGS. 1 and 4)which is rotatably fitted into a circular aperture 10a formed in thebase 10. At the upper end of its central passage, member 31 carries ametal bush 32 rotatably fitted into a circular aperture 33'a provided ina metal bridge piece 33' fixed to the wall 12 of the casing thisaperture 33a being located directly above the aperture 10a in base 10.Spring washers 34a and 34b assist in maintaining the tubular member 31in a predetermined axial position.

As shown in detail in FIG. 7, member 31 is formed in its wall with alongitudinally extending slot 35 having relatively close parallel edgesat its upper part 35a, the width of the lower part 3512 being aboutthree times that of the upper part 35a.

In front of this slot 35, member 31 carries a resilient metal blade 36which is secured to this member a screw 36:: and which contacts bush 32via this screw. The blade 36 is thus connected electrically to thebridge piece 33' via the bush 32 and the spring washer 34b.

As can be seen from FIGS. 4 and 5, the blade 36 is formed with a bentpart 36b near its lower end, this bent part projecting into the slot =35of member 31 when blade 36 is at rest. Moreover, the lower end portionof blade 36 is engaged in an annular recess 29a formed in the top sideof a gear 29. When the blade 36 is in its rest position as shown in FIG.5 it occupies a radially innermost position, out of contact with gear29, and when the blade 36 is flexed radially outwardly, away from itsrest position, it comes into contact with gear '29, this outward flexingmovement of blade 36 being brought about by a pushmember 37 whichprojects through the slot 35 and comes to bear against the bent part 36bof the blade as shown in FIG. 4.

As the gear 29 is electrically connected to the bridge piece 33 by thespring washer 3 4b, it will be appreciated that when the resilient blade36 is moved into the flexed position shown in FIG. 4, the bridge piece33' and 33" are connected together electrically whereas they are cuttion of rest in FIG. 5.

Blade 36 and the inner surface of the recess 29a: in gear 29 thus act asthe movable contact and as the stationary contact of an electric currentswitch which is identified by a reference I in the FIG. 8 circuitdiagram and which is placed between one terminal of the synchronousmotor M for driving the apparatus and one pole of the switch 13 forcontrolling the supply of electric current to the apparatus.

In this connection, it will be observed from FIGS. 2 and '8 that thebridge piece 33' is linked by a connection p firstly to the motor M andsecondly to one side of a compensating capacitor C. As for the bridgepiece 33" it is linked by a connection q to the movable contact ofswitch 13.

Motor M and the other side of capacitor C are linked by a connection Into one of the lines, V, of a single phase a.c. supply, whereas thestationary contact of switch 13 is linked by a connection 11 to theother line, 0, of the supply.

As can be seen from FIGS. 4 and 5 of the accompanying drawings, thepush-member 37, made of plastic material, is mounted on a pin 38 whichextends axially through the tubular member 31 and which is slidablymounted in the root portion 31a thereof and in a bush 39 of plasticmaterial which is mounted with a tight fit in the metal bush 32. Besidesthis axial movement, the pin 38 can also perform a slight angularmovement, the extent of this movement being limited by the engagement ofthe pushmember 37 with either of the longitudinal edges of slot 35 alongthe wider part 35a thereof. The two extreme angular positions that thepush-member 37 can occupy in this part 35a of slot 35 can be seen fromFIG. 6, these two positions determining the extent to which pin 38 canturn. In the first of these positions, push-member 37 is drawn in fulllines whereas in the second position pushrnember 37 is drawn inchain-dotted lines and is identifie as 37'.

Pin 38 can be moved to either of two extreme axial positions in relationto the tubular member 31, i.e. a first, uppermost, position, not shown,in which the pushmember 37 comes to bear against the top edge of slot 35and a second, lowermost, position, shown in FIGS. 4 and 7, in Which thepush-member 37 comes to bear against the bottom edge of slot 35. It isto be noted that it is only when the pin 38 occupies simultaneously boththis second extreme axial position and its first extreme angularposition that the tip of push-member 37 can engage the most inwardlyprojecting portion of the bent part 36b of blade 36, and that it is onlyunder these conditions that the tip of blade 36 will come into contactwith gear 39. Furthermore, since the edges along the wider part 35a ofslot 35 are spaced apart by a distance slightly greater than the widthof push-member 37 it will be appreciated that not only will thepush-member slide freely between these edges, for instance when the pin38 is being: moved from its uppermost position to its lowermostposition, but also that this sliding movement will take place with thepin 38 being kept in its first extreme angular position.

Moreover, during sliding movement, the push-member 37 normally remainsout of engagement with the blade 36 over the major part of its travelbetween the top and bottom edges of slot 35 and the push-member 3-7 onlycomes into contact with the blade 36 when it reaches the.

immediate vicinity of the bent part 36b of the latter so that the switchI can only be closed when the blade 36 and the push-member 37 occupy therelative positions visible in FIG. 4 (corresponding to the lowermostposition of pin 38).

When the switch I is closed, the pin 38 can only be moved out of itsfirst angular position to its second angular position by exerting on pin38 a torque having a direction w (FIG. 6), the intensity of the torquebeing directly dependent on the elastic force exerted by the flexedblade 36 on the push-member 37 and on the amount of frictionalresistance therebetween. As will be explained later,

this elastic force is carefully chosen in dependence on thecoagulometric test which the illustrated apparatus is required toperform.

To enable the pin 38 to be moved from its first extreme axial positionto its second extreme axial position, or vice versa, pin 38 carries atits top end a disc 40 (FIG. 1) engaging in a slot 27a made in the arm 27that is secured to the rod 23, thus rendering pin 38 kinematically rigidwith rod 23.

The lower end of this pin is shaped to form a lancet 38a and carries acap 41, the opening of which has a crosssection slightly greater thanthat of the rod 3 of a container device of the kind visible in FIGS. 9to 11. The lancet 38a is in fact intended to be driven into the upperend of said rod, as will be indicated below, the cap serving to coverthis end so as to provide lateral guidance of the rod during the drivingin operation of the lancet into the rod.

The right hand end of the shaft 26 (FIG. 3) carries a bevel pinion 42meshing with a wheel 43 rotatably mounted on a vertical shaft 44. Onthis shaft 44 is secured an arm 45 carrying a pivotal pawl 46 which isheld by a spring 47 in permanent contact with the teeth of a wheel 48. Asecond pawl 49, which is subjected to the action of a spring 49a,prevents any rotation of the wheel 48 in an anticlockwise direction(BIG. 2).

The wheel 48 is keyed on the upper end of a hollow shaft 50 rotatablymounted in a bearing 51 fitted into an aperture 10b formed in the base10 and secured to the latter.

At its lower end, the shaft 50 carries a metal plate 52, for example ofaluminium, from the upper face of which project ten equidistantly spacedcylindrical bosses 52a. Each of these bosses has a diameter and a heightrespectively corresponding to the diameter and depth of the recessprovided in the lower portion of element 2 of a container device,between the disc 5 and the free end of this element (FIG. 9).

In the plate 52 is arranged an annular electrical resistor R (FIGS. 3and 8) which is suitably insulated in relation to plate 52 and whichserves to heat this plate in order to maintain it at a temperature of 37C. The supply of this resistor is effected by electrical conductors 53extending through the shaft 50 and by four contact rings 55 of which thelowermost two are connected to said conductors and which are carried bya sleeve 54 of insulating material which is secured to the upper end ofthis shaft.

In one of the bosses 52a is also mounted a thermocouple T which isconnected to a switching box 58 (FIGS. 2 and 8) by means of twoconductors 57 which also extend through the hollow shaft 50 and whichlead to the two uppermost rings 55 of sleeve 54 (FIG. 3). A pair ofsliding contacts 59 connect the rings that are associated with thethermocouple T to the switching box 58. In a similar manner, a secondpair of sliding contacts 60 connect the rings to which are connected theconductors 53 for the resistor R, one to this same switching box, andthe other, via connections r and m, to the line V of the electricalsupply for the apparatus. The switching box 58 is moreover connected tothe switch 13 via a connection 2 (FIGS. 2 and 8). This switching box 58is arranged in such a way as to control the supply of current to theresistor R so long as the thermocouple T indicates that the plate 52 hasa temperature lower than 37 (3., whereby the devices that contain theblood to be tested and the reactants (thromboplastine and CaCl and thatare placed on this plate will be kept at this temperature throughout thetest.

Before fully describing the operation of the described apparatus, itshould further be noted that:

(a) The location of the hollow shaft 50 and the dimensions of the plate52 are such that, when this plate rotates, the various container devicescarried thereby successively come to lie in alignment with the pin 38,below the latter;

(b) The number of teeth on the wheel 48 is equal to the number of bosses52a on plate 52;

(c) When the rod 23 is in its lowermost position, as in FIG. 3, the pawl47 is in a retracted position, shown by chain-dotted lines in FIG. 2,this pawl moving to the position shown in full lines, having regard tothe various gear reductions which take place, only when the rod 23 hasbeen lifted into a position corresponding to the first extreme axialposition (i.e. the uppermost position) of the pin 38; in thisconnection, the plate 52- can only be driven in the direction F (FIG. 2)as it is prevented from moving in the opposite direction by the pawl 49;the pawl 46 thus jumps over the teeth of the wheel 48 when it isreturned to the position shown in chain-dotted lines;

(cl) The length of the pin 38 is such that, in its first extreme axialposition (i.e. the uppermost position), the lancet 38a of pin 38 liesabove the level of the top edges of the container devices carried byplate 52, thereby enabling the latter to be rotated in direction F Inorder to use the described apparatus, the rod 23 is first raised thusopening the switch I (FIG. 8), the pushmember 37 being moved above thebent part 36b of blade 36 and the latter moving to its inoperative,rest, position, away from the gear 29 (FIG. the switch 13 is then closedso as to feed current to the resistor R in plate 52 and to heat thisplate to 37 C. On the plate 52 are then arranged ten container devices,each one containing, as described, firstly a metered quantity of amixture of blood and of thromboplastine suspension in trisodium citratesolution, and secondly a metered quantity of sodium chloride solution,these metered quantities having all previously been heated to atemperature of 37 C., for instance by placing these devices in anatmosphere having that temperature.

At this point, the counter 18 reads zero and the motor M is at a stop.The rod 23 is then moved to its lowermost position, shown in FIGS. 1 and3. As the pin 38 is kinematically rigid with the rod 23, and as its capextends slightly above one of the container devices carried by the plate52, the action of moving the rod 23, in the manner indicated, firstcauses the lancet 38a of pin 38 to be driven into the upper end of therod 3 of the container device lying therebeneath (-FIG. 9). Then, as thedownward movement of the rod 23- continues, the pin 38 exerts on the rod3 of this container device an axial thrust in direction F (FIG. 9),which, if it is sufliciently strong, causes the weak annular membranethat connects the rod 3 to the tubular element 1 of the device, tobreak, thus causing the stirring end of the rod 3 to be pushed intoenclosure E Once through enclosure E rod 3 engages disc 4 (FIG. 10) andtransmits to the latter a force which, if strong enough, causes theannular membrane 2d that connects disc 4 to the tubular element 2 tobreak also so that the stirring end of rod 3 also pentrates into theenclosure E of the container device, which enclosure contains thesolution of calcium chloride.

When the rod 23 reaches its lowermost position (FIGS. 1 and 3), the pin.38 and the rod 3 which is fixed to pin 38 occupy the position seen inFIG. 11, in which position the push-member 3-7, that is rigid with pin38, presses the blade 36 against the gear wheel 29', thereby closing theswitch I. The motor M then begins to rotate to drive with synchronousspeed the counter 18, the tubular member 31, the pin 38 and hence alsothe rod 3 that is secured to the lower end of the pin 38.

But from the moment when the calcium chloride solution has been able tomix with the mixture of trisodium citrate solution, thromboplastine andblood, i.e. from the moment when the partition constituted by the disc 4has yielded, the liquid mixture in the container device begins tocoagulate, becomes more and more viscous and tends to oppose to agreater and greater extent the rotary movement imparted to the rod 3 andtherefore the rotation of the pin 38. At a certain instant, the brakingaction that is exerted by the coagulated mixture becomes greater thanthe holding action of blade 36 on push-member 37. As a result pin 38 ispivoted into its second extreme angular position and the push-member 37comes to occupy the disengagement position 37' visible in FIG. 6; theblade 36 then ceases to be in contact with the gear wheel 29 and themotor M stops, as also the counter 18.

The numerical indication given by the drums 1-9 of the counter 18 isindicative of the number of revolutions which the motor M has performedsince the beginning of this particular operation and hence of the timethis operation has taken, since the motor M is a synchronous motorhaving a substantially constant rotational speed.

It is thus by reading this numerical indication that it becomes possibleto deduce, in each case, whether the tested samples of blood have normalcoagulation factors or not.

When a counter reading is finished, the rod 23 and its associated pin 38are raised, thereby enabling the pin 38 to be released from the rod 3 ofthe container device that has hardlybeen used for the coagulometry test,the said rod being held back in the container device by the coagulatedmass filling enclosures E and E thereof.

By virtue of this upward movement of the rod 23, the plate 52 is alsocaused to rotate through an angle such as to bring below the pin 38 thesecond of the ten container devices which this plate carries. It shouldbe pointed out at this juncture that the angular displacement of plate52 does not take place throughout upward vertical movement of the rod23, but only after the latter has effected about 40% of its travel. Itis indeed essential for the pin 38 to be almost out of the containerdevice which has just been used to carry out the test so that the deviceshould not strike the pin when the plate 52 begins its angular movement.This time lag in the actuation of the plate is achieved by giving thepawl 47 a path of travel greater than the length of the pitch of theteeth on the wheel 48 but less than double this pitch. This path oftravel may be about 1.8 times the pitch if the locking pawl 49 is incontact with the radial flank of a tooth when the pawl 46 is in theposition shown in full lines, i.e. at the end of its path of travelduring the driving phase thereof. In its second, inoperative, positionshown in chaindotted lines in FIG. 2 (retracted position of the pawl),the pawl 46 will be distant from the radial flank of the tooth, againstwhich it will subsequently be required to bear, by a lengthsubstantially equal to 0.8 times the pitch of the teeth. It will thus beappreciated that, in order to drive the wheel 48 and hence the plate 52in direction F the pawl must first travel a non-activating distance,while remaining in contact with the edge of the tooth preceding that itis required to push. It is during this time when the pawl 45 does notdrive the plate 52, that the pin 38 moves out of the container devicewhich has just been used for the performance of a test.

It is to be noted that in carrying out blood coagulation tests otherthan the Quick or Soulier test, the thromboplastine solution may bereplaced by a solution of at least one other coagulant factor. Thus, inorder to carry out a Stypven test, for showing up abnormality of thefactors II, V and X only, and especially the last of these factors, thethromboplastine suspension is replaced by a solution containing forexample viper venom. In such a case, the coagulation time is of theorder of 13 to 14 seconds.

I claim:

1. An apparatus for measuring the coagulation time of blood samplescontained in capsules, said apparatus comprising a housing, drive meanswithin said housing, an elongated shaft mounted for rotation within saidhousing and extending through a portion of said housing and dependingtherefrom, a non-conducting tubing means surrounding and engaging thatportion of said shaft contained within said housing and adapted torotate therewith, said drive means operatively connected to said tubingmeans to rotate said tubing and said shaft, circuit means associatedwith said drive means and said tubing means, and a cam means slidablyconnected to that portion of said shaft contained within said housingnormally keeping said circuit means closed to provide power to saiddrive means and said cam means adapted to break said circuit upon saidshaft encountering a predetermined resistanee caused by said samplebeginning to coagulate and slipping relative to said tubing means, acounter connected between drive means and said shaft means and adaptedto count the number of rotations of said shaft means and means adaptedto raise said shaft and reset said counter simultaneously.

2. An apparatus as in claim 1 wherein the depending Y end of said shaftis tapered to form a lancet, said lancet adapted to engage a stirrer ina capsule containing a blood sample.

3. An apparatus as in claim 2 wherein said lancet has a cap positionedthereon, said cap opening downward and adapted to surround the top of astirrer which is engaged by said lancet.

4. An apparatus as in claim 1 including a longitudinal slot in saidtubing having a widened arcuate portion at its lower end, said cam meanscomprising a member fixed on said shaft and protruding through saidslot, a resilient electrical contact means adjacent said slot and saidcam means normally biasing said contact means to complete said circuitmeans.

5. An apparatus for determining the viscosity of liquid samplescontained in containers comprising a base, a motor, a counter connectedto said motor to count the number of revolutions thereof, indicia onsaid counter translating the number of revolutions of said motor intotime units, vertically slidable means on said base and operativelyconnected to said counter to reset the same, said motor operativelyconnected to a rotatable tubular member and adapted to rotate the same,a shaft journalled for longitudinal movement within said tubular memberand depending below said base for engaging a stirrer located within asample container, said shaft and said vertically slidable means beingoperatively connected to enable the shaft to be raised and lowered,circuit means connected to said motor, and a switch means located on theupper portion of said shaft and adapted to break said circuit when thestirring shaft encounters resistance and slips rotatively relative tosaid tubular member as a result of said sample coagulating upon stirringand said shaft having a lancet means at its lower end for engaging astirrer in a container containing a blood sample.

6. An apparatus as in claim 5 including means for supporting a pluralityof sample containers beneath said stirring shaft, gear means and pawlmeans connecting said vertically slidable means with said containersupporting means to advance said means upon upward movement of saidvertically slidable means.

7. An apparatus as in claim 6 wherein said container supporting meanscomprises a rotatable support member, depending shaft means mountingsaid support member to said base, a second gear means on said shaftmeans cooperating with said pawl means to rotate said support memberwhen said vertically slidable member and said shaft are raised so as toposition the next sample container under said shaft to allow said lancetto engage a stirrer in said container.

8. An apparatus as in claim 6 wherein said vertically slidable member isa rack and said counter has a pinion gear attached thereto engaging saidrack.

9. An apparatus as in claim 6 including heating means located in saidcontainer supporting means for maintaining said containers at apredetermined temperature.

10. An apparatus as in claim 6 wherein said switch means includes avertical slot in said tubular member terminating in a widened portion atthe bottom and a cam member fixed to said shaft and projecting from saidslot, a resilient contact means adjacent said slot and adapted to bebiased by said cam means when said cam means is at the bottom of theslot to close said circuit means when said shaft and tubular member arerotating at the same speed whereby said contact starts said motor whenthe shaft is lowered to engage a stirrer in a container and stops saidmotor when the speed of the shaft slows upon coagulation of said samplein relation to said tubular member thus allowing the cam to movearcuately within said widened slot portion to disengage said contact.

11. An apparatus as in claim 10 wherein said motor is operativelyconnected to said tubular member by a bevel gear and said resilientcontact means is a spring secured to said tubular member and adapted tobe biased into engagement with said bevel gear to close said circuit.

References Cited UNITED STATES PATENTS 3,520,659 7/1970 Steinberg et al.23253 X 3,267,364 8/1966 Page et al. 23230 BX 3,162,038 12/1964 Robersonet al. 73-59 3,440,866 4/1969 Ness et al. 7364.1 2,423,687 7/1947 Daviset al. 73-59 X JOSEPH SCOVRONEK, Primary Examiner U.S. Cl. X.R.

